The present invention relates to the art of intrabody therapy involving application energy to the body and further relates to monitoring of such therapy by magnetic resonance.
Various forms of therapy can be applied within the body of a human or other mammalian subject by applying energy from outside of the subject. In hyperthermia, ultrasonic or radio frequency energy is applied from outside of the subject""s body to heat the tissues. The applied energy can be focused to a small spot within the body so as to heat the tissues at such spot to a temperature sufficient to create a desired therepeautic effect. This technique can be used to selectively destroy unwanted tissue within the body. For example, tumors or other unwanted tissues can be destroyed by applying heat to heat the tissue to a temperature sufficient to kill the tissue, commonly to about 60xc2x0 to 80xc2x0 C., without destroying adjacent normal tissues. Such a process is commonly referred to as xe2x80x9cthermal ablationxe2x80x9d. Other hyperthermia treatments include selectively heating tissues so as to selectively activate a drug or promote some other physiologic change in a selected portion of the subject""s body. Other therapies use the applied energy to destroy foreign objects or deposits within the body as, for example, in ultrasonic lithotripsy.
Magnetic resonance is used in medical imaging for diagnostic purposes. In magnetic resonance imaging procedures, the region of the subject to be imaged is subjected to a strong magnetic field. Radio frequency signals are applied to the tissues of the subject within the imaging volume. Under these conditions, atomic nuclei are excited by the applied radio frequency signals and emit faint radio frequency signals, referred to herein as magnetic resonance signals. By applying appropriate gradients in the magnetic field during the procedure, the magnetic resonance signals can be obtained selectively from a limited region such as a two-dimensional slice of the subject""s tissue. The frequency and phase of the signals from different portions of the slice can be made to vary with position in the slice. Using known techniques, it is possible to deconvolute the signals arising from different portions of the slice and to deduce certain properties of the tissues at each point within the slice from the signals.
Various proposals have been advanced for using magnetic resonance to monitor and guide application of energy within the body. As disclosed, for example, in the U.S. Pat. Nos. 4,554,925, 4,620,546 4,951,688 and 5,247,935, the disclosures of which are hereby incorporated by reference herein, certain known magnetic resonance procedures are temperature sensitive, so that magnetic resonance data acquired using these procedures will indicate changes in temperature of the tissues. For example, a magnetic resonance parameter referred to as T1 or spin-lattice relaxation time will vary with temperature. If magnetic resonance imaging apparatus is actuated to acquire T1 for various volume elements or xe2x80x9cvoxelsxe2x80x9d within the subject, the data for different voxels will vary with temperature, at least within a tissue having generally the same composition. The data can be portrayed as a visible image and hence different temperatures can be shown by the differences in brightness or color within the displayed image. Thus, the location within the body being heated can be monitored by monitoring such a visible image during application of energy to the body. Also, the degree of the heating can be monitored by monitoring T1 for the heated regions. Magnetic resonance parameters other than T1 can be portrayed or monitored in the same way.
Although these procedures have well been known, they have not been widely adopted in the medical community. Magnetic resonance imaging instruments of the types commonly used for medical diagnostic applications include large, precise magnets which are arranged to impose a high magnetic field, typically about one Tesla or more over a relatively large imaging volume typically 10 cm or more in diameter. Certain magnetic resonance imaging static field magnets severely limit access to the subject. For example, a solenoidal air-core superconducting magnet may have superconductive coils surrounding a tubular subject-receiving space. The subject lies on a bed which is advanced into the said tubular space so that the portion of the patient to be imaged is disposed inside of the tubular space. Iron core magnets typically have ferromagnetic frames defining opposed poles and a subject-receiving space lying between the poles. Permanent magnets or electromagnets are associated with the frame for providing the required magnetic flux. Depending upon the design of the magnet, either the superconductive coils or the frame may obstruct access to the patient during operation of the magnetic resonance instrument. Moreover, because the magnetic resonance imaging instruments typically employed in medicine are expensive, fixed structures, there are substantial costs associated with occupancy of the instrument. Because hyperthermia procedures typically require significant time to perform, it is expensive to perform these procedures while the patient is occupying the magnetic resonance imaging instrument. Moreover, because instruments of this type are typically found only in specialized imaging centers and radiology departments of hospitals, use of the magnetic resonance imaging instrument for therapeutic procedures is associated with considerable inconvenience to the patient and to the treating physician. Thus, despite all of the efforts devoted heretofore to MRI-guided hyperthermia procedures and apparatus, there remains a considerable, unmet need for improvements in such procedures and apparatus which would reduce the cost and increase the convenience of such procedures.
Moreover, there has been a need for further improvement in hyperthermia procedures of this type. The physician typically aims the energy-applying device manually and applies so-called xe2x80x9csubthresholdxe2x80x9d doses of energy, sufficient to heat the tissues slightly but insufficient to cause permanent change in the tissue. The physician then observes the location of the heated spot on a magnetic resonance image to confirm that the energy-applying device is aimed at the desired location in the subject""s body.
The response of the tissues within the body to the applied energy varies. Differences in tissue properties such as specific heat and thermal conductivity will cause differences in the change in the temperature caused by absorption of a specific amount of energy. The xe2x80x9csusceptibilityxe2x80x9d or tendency of the tissues to absorb the applied energy also varies from place to place. Therefore, after the device has been aimed onto a particular spot, the physician must apply a therapeutic dose by gradually increasing the amount of the energy applied to the spot and monitoring the degree of temperature change to the spot by means of the magnetic resonance information as, for example, by observing the visually displayed magnetic resonance image.
Typically, the spot heated during each operation of the energy-applying device is relatively small as, for example, a spot about 1 mm-3 mm in diameter. To treat a large region within the subject, the spot must be repositioned many times. All of this requires considerable time and effort. Moreover, the procedure is subject to errors which can cause damage to adjacent organs. For example, thermal energy is commonly applied to treat benign prostatic hyperplasia or tumors of the prostate gland. If the physician mistakenly aims the energy-applying device at the urethra and actuates it to apply a therapeutic dose, the delicate structure of the urethra can be destroyed. Therefore, improvements in thermal energy treatments which improve the safety of such treatments and reduce the effort required to perform such treatments, would be desirable.
The present invention addresses these needs.
One aspect of the present invention provides therapeutic apparatus. Apparatus according to this aspect of the invention desirably includes a movable static field magnet adapted to apply a static magnetic field in a magnetic resonance volume at a predetermined disposition relative to the static field magnet and also includes an energy applicator adapted to apply energy within an energy application zone at a predetermined disposition relative to the applicator. Apparatus according to this aspect of the invention also includes positioning means for moving the static field magnet and the energy applicator to position the magnet and the applicator so that the magnetic resonance volume at least partially encompasses a region of the subject to be treated and so that the energy application zone associated with the applicator intersects the magnetic resonance volume within the region of the subject to be treated. Preferably, the apparatus includes a chassis and both the static field magnet and the energy applicator are mounted to the chassis. The positioning means in this case includes means for moving the chassis so as to position the chassis relative to the subject. The static field magnet desirably is a single-sided static field magnet arranged so that the magnetic resonance volume is disposed outside of the static field magnet and spaced from the static field magnet in a forward direction. The static field magnet most preferably is substantially smaller than the static field magnets utilized in conventional magnetic resonance imaging instruments. For example, the static field magnet may have dimensions of a meter or less and may be light enough to be moved readily by a positioning device of reasonable cost and proportions. Thus, the entire apparatus can be moved as required to position it adjacent to the region of the subject""s body which requires treatment. The most preferred apparatus according to this aspect of the present invention is small enough and inexpensive enough to be used in a clinical setting such as a physician""s office or medical center. Thus, it is feasible to perform magnetic resonance-monitored energy applying procedures in a normal clinical setting. There is no need to occupy an expensive diagnostic magnetic resonance imaging instrument during such procedures.
Additional aspects of the present invention provide improved single-sided static-field magnets for magnetic resonance. Even with such improvements, however, the small single-sided static field magnet typically is capable of providing a magnetic field suitable for magnetic resonance imaging only in a relatively small magnetic resonance volume as, for example, a magnetic resonance volume with dimensions of a few centimeters. Such a small imaging volume normally would be regarded as undesirable in an instrument for general purpose magnetic resonance imaging purposes. However, instruments according to this aspect of the present invention incorporate the realization that energy-applying procedures are applied within relatively small regions of the subject""s anatomy, so that an instrument with a small magnetic resonance volume still can provide useful information for controlling the energy-applying procedures. Moreover, the image quality which is required for control of energy application is less than that which is required in diagnostic MRI imaging. The use of a relatively small magnetic resonance volume then permits use of a single-sided magnet which is relatively small, light weight and inexpensive.
Apparatus according to this aspect of the invention desirably also includes ancillary equipment such as gradient coils for applying a magnetic field gradient within the magnetic resonance volume. The gradient coils may be mounted to the chassis or otherwise secured in position relative to the static field magnet. The apparatus may also include radio frequency equipment for applying radio frequency signals to the subject and receiving the resulting magnetic resonance signals, as well as devices for actuating the gradient coils to apply the field gradients. The apparatus may further include a computer for processing the magnetic resonance signals such as to derive an image of tissues of the subject within the magnetic resonance volume in working frame of reference such as the local magnetic resonance frame of reference, the frame of reference of the static field magnet. The computer can also process the magnetic resonance signals to derive temperatures of tissues of the subject at one or more locations in the working frame of reference.
The energy applicator may include an array of ultrasound-emitting transducers and may also include a flexible fluid container mounted between the ultrasound transducer array and the energy application zone so that the flexible fluid container can be engaged between the transducer array and a surface of the subject""s body. In a particularly preferred arrangement, the energy applicator includes a mounting and the array of transducers and the flexible fluid container are provided as a disposable unit releasably coupled to the mounting. Stated another way, the permanent component of the apparatus may include, as the energy applying device, a mounting suitable for receiving such a disposable unit. Typically, the mounting provides electrical connections for the transducer array and also provides mechanical securement for the disposable unit. In a particularly preferred arrangement, the apparatus includes a radio frequency antenna in the form of a loop for transmitting or receiving RF signals. The antenna is secured in position to the mounting so that when the ultrasonic transducers array and flexible fluid container are secured to the mounting, the antenna encircles the flexible fluid container at or near the surface of the patient""s body. The static field magnet is typically arranged to provide a magnetic field directed in an axial direction, along a central axis. Desirably, the energy applicator and RF antenna are positioned so that an applicator axis extending from the applicator into the overlapping portions of the energy application volume and magnetic resonance volume is transverse to the central axis of the static field magnet. The RF loop antenna axis is also transverse to the central axis of the static field magnets. As further discussed below, this arrangement is convenient to use and also enhances the interaction between the transmitted RF signals and the atomic nuclei in the imaging volume as well as the signal to noise ratio of the received magnetic resonance signals.
A further aspect of the invention provides magnetic resonance apparatus, in particular, imaging apparatus incorporating movable single-sided static field magnets and positioning devices as discussed above. Magnetic resonance apparatus according to this aspect of the invention may serve as a component of the treatment apparatus as may also be used independently to provide images of regions in the subject for other purposes.
A further aspect of the present invention provides methods of treating living subjects, such as a human or other mammalian subject. Methods according to this aspect of the invention include the steps of positioning a movable static field magnet adapted to apply a static field in a magnetic resonance volume, the magnet being positioned relative to the subject so that the magnetic resonance volume at least partially encompasses a region of the subject to be treated. A movable applicator adapted to apply energy within an energy application zone is positioned relative to the subject so that the energy application zone intersects the magnetic resonance volume within the region of the subject requiring treatment. While the static field magnet is applying the static magnetic field in the magnetic resonance volume, radio frequency signals are applied so as to elicit magnetic resonance signals from tissues of the subject in the magnetic resonance volume. The method further includes the step of receiving these magnetic resonance signals and deriving magnetic resonance information relative to the subject""s tissues in the magnetic resonance volume from the magnetic resonance signals. Further, the method includes the step of actuating the movable energy-applying device to apply energy to tissues of the patient in the energy application zone so as to treat the tissues and controlling one or more parameters of the treatment by use of the magnetic resonance information.
As mentioned above in connection with the apparatus, the use of movable static field magnets and energy applicators allow these devices to be positioned relative to the patient. Here again, it is preferred to use a static field magnet and energy applicator which are mounted to a common chassis, so that the positioning steps include the step of moving the chassis so as to position the chassis relative to the subject. The chassis may be moved after the procedure so as to reposition the magnetic resonance volume and energy application zone in a new region of the subject and the remaining steps of the procedure may be repeated so as to treat the tissues in a new region. The methods according to this aspect of the invention also include the realization that because the treatment procedure is localized, it can be performed using a magnet with a relatively small magnetic resonance volume.
Most preferably, the magnetic resonance signals are spatially encoded, and the step of deriving magnetic resonance information is performed so as to derive magnetic resonance information at one or more points within the magnetic resonance volume, the points having locations defined in the local magnetic resonance frame of reference. The parameter or parameters of the treatment which are controlled using the magnetic resonance information may include the location of the treated tissues. Thus, the monitoring step may include the step of controlling the location of the treated tissues in a working frame of reference which is correlated to the local magnetic resonance frame of reference. Thus, the step of controlling the location of the treated tissue may include the step of aiming the energy applicator so as to apply the energy at one or more treatment locations having positions defined in the working frame of reference. The aiming procedure may involve either moving the applicator or, in the case of a phased array applicator, adjusting the phases and amplitudes of the signals supplied to the elements of the array. The method may farther include the step of displaying an image of the subject""s tissues in a working frame of reference, desirably the local magnetic resonance frame of reference. The image desirably is derived in whole in part from the magnetic resonance information obtained by use of the movable static field magnet and associated components. The aiming step may be performed at least in part by inspection of the image as, for example, by observation of a representation of the aim of the energy applicator superposed on the image.
According to a further aspect of the invention, a method of treating a mammalian subject may include the step of selecting a treatment volume within the subject having boundaries defined in a working frame of reference.
A method according to this aspect of the invention may also include the steps of actuating the applicator to apply energy at a plurality of test points in or adjacent the treatment volume and determining a degree of heating of the tissue at each such test point resulting from such actuation. Most preferably, the method further includes the step of deriving a relationship between energy applied by the applicator and degree of heating for a plurality of treatment locations within the treatment volume from the degrees of heating of the test points and the energy applied by the applicator to the test points. A method according to this aspect of the invention desirably further includes the step of actuating the applicator to apply energy at the treatment locations, the amount of energy applied by the applicator in this step at each such treatment location being selected at least in part on the basis of the relationship between energy and heating for such treatment location derived in the aforesaid steps. This method may be used in magnetic resonance-guided hyperthermia including the aforesaid methods using the movable static field magnet, and other methods. The step of determining degrees of heating for the test points desirably includes the step of acquiring magnetic resonance information for each such test point. The test doses of energy desirably are applied at levels less than a threshold level required to cause permanent change in the tissues at the test points. The step of deriving the energy to heating relationship for the treatment locations desirably includes the step of deriving a relationship between energy supplied and degree of heating for each test point and interpolating between such relationships over distance between the test points. In a particularly preferred arrangement, the boundaries of the treatment volume include one or more polyhedral primitives and the test points are disposed adjacent vertices of the polyhedral primitives. The boundaries may be selected by displaying an image of the subject in the working frame reference encompassing the region to be treated, displaying a visual representation of the boundaries superposed on the image and applying manual inputs to a control element to adjust the boundaries while the visual representation is displayed.
After the boundaries have been established, some or all of the remaining steps desirably are performed automatically. Thus, the step of actuating the applicator to apply the therapeutic energy at the treatment locations may be performed by automatically adjusting the aim of the applicator to different treatment locations within the preset boundaries according to a preselected sequence such as a sequential raster scan or a pseudorandom pattern and automatically operating the applicator to apply the appropriate therapeutic dose. Methods according to this aspect of the present invention greatly facilitate the therapeutic process. They provide good control over the therapy and compensation for the varying response to applied energy at different points within the body while greatly minimizing the time spent in determining the susceptibilities at various points and the effort required to perform the procedure.
Yet another aspect of the present invention provides a method of therapy including the steps of defining an avoidance zone encompassing the tissues of the subject which are not to be subjected to treatment in a working frame of reference and recording the boundaries of the avoidance zone. A method according to this aspect of the invention also includes the step of operating an intrabody treatment device such as an energy applicator by manually moving an aim point of the treatment device relative to the subject and manually actuating the treatment device to apply a treatment at the aim point. Methods according to this aspect of the invention also include the step of tracking the aim point in the working frame of reference during the manual operation step and automatically controlling operation of the treatment device so as to preclude application of the treatment in the avoidance zone. The step of automatically controlling operation may include the step of automatically inhibiting movement of the aim point into the avoidance zone. For example, the step of manually moving the aim point may include the step of manually moving an actuator such as a joystick and the step of automatically inhibiting movement of the aim point may include the step of providing force feedback opposing movement of the actuator in a direction corresponding to movement of the aim point into the avoidance zone when the aim point is near the avoidance zone. Alternatively or additionally, the step of automatically controlling operation of the treatment device may include the step of inhibiting application of the treatment when the aim point is in the avoidance zone. For example, where the treatment device is an energy applicator, the automatic control may inhibit application of energy if the aim point is in the predefined avoidance zone. The avoidance zone may be defined in a manner similar to the treatment volume discussed above, i.e., by displaying a visual representation of the image of the subject and displaying a visual representation of the boundaries of the avoidance zone superposed on such image while applying manual inputs to a control element to adjust the boundaries. Methods according to this aspect of the present invention provide greatly enhanced safety in manually controlled therapeutic procedures such as thermal ablation of tissues. These and other features and advantages of the present invention would be more readily apparent from the detailed description of the preferred embodiments set forth below, taken in conjunction with the accompanying drawings.